Sooty mangabeys naturally infected with simian immunodeficiency virus (SIV) do not develop immunodeficiency despite the presence of viral loads of 105 to 107 RNA copies/ml To investigate the basis of apathogenic SIV infection in sooty mangabeys, three sooty mangabeys and three rhesus macaques were inoculated intravenously with SIVmac239 and evaluated longitudinally for one year SIVmac239 infection of sooty mangabeys resulted in 2 to 4 log lower viral loads than in macaques and did not reproduce the high viral loads observed in natural SIVsmm infection During acute SIV infection, polyclonal CTL activity coincident with decline in peak plasma viremia was observed in both macaques and mangabeys Eight to 20 weeks later, CTL activity declined in the macaques but was sustained and broadly directed in the mangabeys Neutralizing antibodies to SIVmac239 were detected in the macaques but not the mangabeys Differences in expression of CD38 on CD8+ T lymphocytes or in t he percentage of naive phenotype T cells expressing CD45RA and CD62L-selectin did not correlate with development of AIDS in rhesus macaques In macaques, the proportion of CD4+ T lymphocytes expressing CD25 declined during SIV infection, while in mangabeys, CD25-expressing CD4+ T lymphocytes increased Longitudinal evaluation of cytokine secretion by flow cytometric analysis of unstimulated lymphocytes revealed elevation of IL-2 and interferon gamma in a macaque and only IL-10 in a concurrently infected mangabey during acute SIV infection Differences in host responses following experimental SIVmac239 infection may be associated with the divergent outcome in sooty mangabeys and rhesus macaques REFERENCES Kaur A, Grant RM, Means RE, McClure H, Feinberg M, Johnson RP Diverse host response and outcome following SIVmac239 infection in sooty mangabeys and rhesus macaques J Virol 1998; 72:9597-9611